Matches in SemOpenAlex for { <https://semopenalex.org/work/W2888334890> ?p ?o ?g. }
Showing items 1 to 51 of
51
with 100 items per page.
- W2888334890 abstract "Despite the success of antiretroviral therapy (ART) that drastically decreased the deaths of acquired immunodeficiency syndrome (AIDS), human immunodeficiency virus (HIV)-infected patients remain at higher risk for non-AIDS comorbidities than the normal population, especially cardiovascular (CV) diseases. As this population ages with significantly prolonged lifespans by ART, these commonly age-related CV events are becoming more of a pressing issue. A growing body of evidence show that the increased CV risk in HIV patients is driven both by a hypercoagulable state and HIV-associated chronic immune activation and inflammation. However, the exact mechanism remains unclear.In this dissertation, we examined the link between hypercoagulation and immune activation and inflammation, and identified tissue factor (TF) as a critical mediator between the two. We found that a subset of CD14+ monocytes highly express TF during chronic HIV and pathogenic simian immunodeficiency virus (SIV) infection, and was not normalized even after ART. This subset of TFpos monocytes not only triggers activation of Factor X, thus initiating the coagulation cascade, but also is capable of producing multiple inflammatory cytokines upon thrombin stimulation via protease activated receptor-1 (PAR-1) signaling. In vivo blockade of TF in acutely SIV-infected pigtail macaques (PTMs) by an innovative TF inhibitor, Ixolaris, resulted in reduction of coagulation marker D-dimer levels as well as markers of immune activation and inflammation. We also administered a direct thrombin inhibitor (dabigatran) and PAR-1 inhibitor (vorapaxar) in SIV-infected PTMs and monitored a large array of biomarkers related to hypercoagulation and immune activation and inflammation in all three treatment groups. Dabigatran and vorapaxar also induced reduction of both hypercoagulation and immune activation and inflammation, although not to the extent of Ixolaris, and may have impacted different aspects of HIV/SIV pathogenesis. Altogether, these results point to a critical role of TF in bridging hypercoagulation and immune activation and inflammation to fuel HIV-associated comorbidities, and therapeutically targeting TF-related coagulation pathways is beneficial in reducing the risk of these comorbidities." @default.
- W2888334890 created "2018-08-31" @default.
- W2888334890 creator A5070667482 @default.
- W2888334890 date "2018-04-19" @default.
- W2888334890 modified "2023-09-27" @default.
- W2888334890 title "Coagulation Abnormalities Play a Central Role in HIV Comorbidities and Should Be Therapeutically Targeted" @default.
- W2888334890 hasPublicationYear "2018" @default.
- W2888334890 type Work @default.
- W2888334890 sameAs 2888334890 @default.
- W2888334890 citedByCount "0" @default.
- W2888334890 crossrefType "journal-article" @default.
- W2888334890 hasAuthorship W2888334890A5070667482 @default.
- W2888334890 hasConcept C203014093 @default.
- W2888334890 hasConcept C2776914184 @default.
- W2888334890 hasConcept C2908647359 @default.
- W2888334890 hasConcept C71924100 @default.
- W2888334890 hasConcept C8891405 @default.
- W2888334890 hasConcept C99454951 @default.
- W2888334890 hasConceptScore W2888334890C203014093 @default.
- W2888334890 hasConceptScore W2888334890C2776914184 @default.
- W2888334890 hasConceptScore W2888334890C2908647359 @default.
- W2888334890 hasConceptScore W2888334890C71924100 @default.
- W2888334890 hasConceptScore W2888334890C8891405 @default.
- W2888334890 hasConceptScore W2888334890C99454951 @default.
- W2888334890 hasLocation W28883348901 @default.
- W2888334890 hasOpenAccess W2888334890 @default.
- W2888334890 hasPrimaryLocation W28883348901 @default.
- W2888334890 hasRelatedWork W105218539 @default.
- W2888334890 hasRelatedWork W151256503 @default.
- W2888334890 hasRelatedWork W2002697587 @default.
- W2888334890 hasRelatedWork W2026098592 @default.
- W2888334890 hasRelatedWork W2037143540 @default.
- W2888334890 hasRelatedWork W2053823009 @default.
- W2888334890 hasRelatedWork W2069148320 @default.
- W2888334890 hasRelatedWork W2070036973 @default.
- W2888334890 hasRelatedWork W2085036275 @default.
- W2888334890 hasRelatedWork W2092350992 @default.
- W2888334890 hasRelatedWork W2100203916 @default.
- W2888334890 hasRelatedWork W2113308383 @default.
- W2888334890 hasRelatedWork W2414367013 @default.
- W2888334890 hasRelatedWork W2765222136 @default.
- W2888334890 hasRelatedWork W2798782211 @default.
- W2888334890 hasRelatedWork W3095349290 @default.
- W2888334890 hasRelatedWork W3137612794 @default.
- W2888334890 hasRelatedWork W3140197987 @default.
- W2888334890 hasRelatedWork W316464541 @default.
- W2888334890 hasRelatedWork W3202858575 @default.
- W2888334890 isParatext "false" @default.
- W2888334890 isRetracted "false" @default.
- W2888334890 magId "2888334890" @default.
- W2888334890 workType "article" @default.